Abstract
Benefiting from the continuously clarifying underlying biology of immune checkpoints and ligand–receptor interactions, the emergence of new anticancer treatment strategy, immunotherapy has shown substantial benefits on several liquid and solid tumors. Immune checkpoint inhibitors (ICIs) can block the negative regulatory components and enhance the T cell function, thus leading to prominent anticancer activity. On account of their promising effect on various malignancies shown in clinical trials, ICIs have been considered to be the most potent anticancer agents in the near future. Head and neck cancer is the seventh most common neoplasm worldwide, and the gross 5-year survival rate was only 60%. Managing locoregionally advanced, recurrent, or metastatic head and neck tumors is still a challenging problem for both oncologists and surgeons. Recent clinical trials employing the immune-modulating antibodies that target cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death 1 (PD-1) herald a new era of anticancer therapy. However, like all other anticancer drugs, ICIs also have side effects while upregulating the immune system to enhance antitumor response, which were known as immune-related adverse events (irAEs). Generally, most irAEs were transient, but sometimes they can cause serious organ dysfunction, even fatal. In addition, due to the distinct anatomical feature, advanced head and neck tumors often affect the upper aerodigestive tract and cause serious dyspnea or dysphagia. Toxicities of ICIs may be more lethal for such patients. Thus, with the increasing application of anti-checkpoint agents in head and neck cancer, there is urgent need to ascertain the safety of this novel treatment strategy. Here, we compile this review of existing clinical trials on the toxicity of ICIs during cancer treatment. The particular clinical manifestation, characteristics of complication development in fatal cases, and the management strategies were discussed. This may provide vital information for future oncology trials and clinical practice.
Highlights
Head and neck cancer is the seventh most common neoplasm worldwide, and the gross 5-year survival rate was only 60% (Torre et al, 2015)
Treatment with Immune checkpoint inhibitors (ICIs) improved the overall survival in patients with head and neck squamous cell carcinoma (HNSCC) and improved quality of life compared with the concurrent chemotherapy and radiation therapy (Porceddu and Haddad, 2017; Ribas and Wolchok, 2018)
Higher rates of endocrine disorders are associated with anti-programmed cell death 1 (PD-1) therapy, whereas gastrointestinal toxicities are more common with cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) inhibitor administration
Summary
Head and neck cancer is the seventh most common neoplasm worldwide, and the gross 5-year survival rate was only 60% (Torre et al, 2015). The ICIs that have been tested on HNSCC include PD-1 (nivolumab and pembrolizumab), PD-L1 (atezolizumab, durvalumab, and avelumab), and CTLA-4 (ipilimumab and tremelimumab) (Alsaab et al, 2017; Szturz and Vermorken, 2017; Dogan et al, 2018; Gong et al, 2018) Despite their therapeutic promise and benefits, treatments with ICIs are associated with the onset of immune-related adverse events (irAEs) on account of facilitating autoimmune activity against tumor cells and any organs of the body. After a comprehensive retrieval of online databases including Pubmed, ISI, and clinicaltrials.gov, there were eight clinical trials that use ICI agents to treat HNSCC
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